Retinal ganglion cells downregulate gene expression and lose their axons within the optic nerve head in a mouse glaucoma model

Ileana Soto, Ericka Oglesby, Brian P. Buckingham, Janice L. Son, Elisha D.O. Roberson, Michael R. Steele, Denise M. Inman, Monica L. Vetter, Philip J. Horner, Nicholas Marsh-Armstrong

Research output: Contribution to journalArticle

206 Scopus citations

Abstract

Little is known about molecular changes occurring within retinal ganglion cells (RGCs) before their death in glaucoma. Taking advantage of the fact that γ-synuclein (Sncg) mRNA is expressed specifically and highly in adult mouse RGCs, we show in the DBA/2J mouse model of glaucoma that there is not only a loss of cells expressing this gene, but also a downregulation of gene expression of Sncg and many other genes within large numbers of RGCs. This downregulation of gene expression within RGCs occurs together with reductions in FluoroGold (FG) retrograde transport. Surprisingly, there are also large numbers of Sncg-expressing cells without any FG labeling, and among these many that have a marker previously associated with disconnected RGCs, accumulation of phosphorylated neurofilaments in their somas. These same diseased retinas also have large numbers of RGCs that maintain the intraocular portion while losing the optic nerve portion of their axons, and these disconnected axons terminate within the optic nerve head. Our data support the view that RGC degeneration in glaucoma has two separable stages: the first involves atrophy of RGCs, whereas the second involves an insult to axons, which causes the degeneration of axon portions distal to the optic nerve head but does not cause the immediate degeneration of intraretinal portions of axons or the immediate death of RGCs.

Original languageEnglish (US)
Pages (from-to)548-561
Number of pages14
JournalJournal of Neuroscience
Volume28
Issue number2
DOIs
StatePublished - Jan 9 2008
Externally publishedYes

Keywords

  • Axonal transport
  • Axonopathy
  • Axoplasmic transport
  • DBA/2J
  • Glaucoma
  • Retinal ganglion cell
  • Synuclein

ASJC Scopus subject areas

  • Neuroscience(all)

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  • Cite this

    Soto, I., Oglesby, E., Buckingham, B. P., Son, J. L., Roberson, E. D. O., Steele, M. R., Inman, D. M., Vetter, M. L., Horner, P. J., & Marsh-Armstrong, N. (2008). Retinal ganglion cells downregulate gene expression and lose their axons within the optic nerve head in a mouse glaucoma model. Journal of Neuroscience, 28(2), 548-561. https://doi.org/10.1523/JNEUROSCI.3714-07.2008